Most Effective Hypertensive Medications that Prevent Nephropathy in Diabetic Patients

25-40% of hypertension patients require only monotherapy to control BP, so choice of right single therapeutic agent is critical.

Albuminuria is defined as the presence of albumin in the urine above a concentration of 30mg/day, or spot protein urine concentration 30mg/g, and can be treated with ACEIs, ARBs, CCBs, or diuretics. The elevated urinary albumin excretion rate (UAE) has been associated with an increased risk of cardiovascular mortality, as well as the progression of CVD, and should be treated aggressively. However, there are many diabetes patients with no presence of protein in their urine who may still benefit from the aforementioned drug therapy.

As of the 2016 guidelines, the American Diabetes Association (ADA) recommends ACEIs and ARBs as the first-line agents for treating hypertension, while the Joint National Committee (JNC) recommends ACEIs, ARBs, CCBs, and thiazide diuretics in non-black diabetic patients. For black patients, JNC recommends using calcium channel blockers or thiazide diuretic classes of medications because of the improved cardio protection. In a study performed by Isaacs et al., researchers analyzed primary literature from 1978 until 2015 that was published in PubMed and Medline databases and compared effectiveness of different groups of drugs in preventing nephropathy in patients without the presence of albuminuria. They looked at the studies that researched treatment options for type 2 diabetes patients with hypertension and no albumin in the urine.

Ultimately, they focused on the results of five studies Chen et al., ABCD post hoc analysis, J-MIND, ROADMAP, and BENEDICT, which included the total of 6,331 participants. They found that ACEIs and ARBs were the most appropriate groups of medications for controlling hypertension and had the added benefit of preventing nephropathy. Chan et al. compared Enalapril 40mg daily with Nifedipine 60 mg daily and found no difference between the groups in prevention of proteinuria. ABCD post hoc analysis compared Enalapril 40 mg daily with Nisoldipine 60 mg daily and found that for the first three years, patients taking Enalapril were better protected from excreting protein in urine, but after three years of treatment, there was no difference in progression of albuminuria between the studied groups. The J-MIND study found that Enalapril 5 mg daily decreased urine albumin excretion (UAE) for the first 18 months as compared to Nifedipine 20 mg daily, but after 24 months, there was no difference between the groups. The ROADMAP study found Olmesartan 40 mg daily superior to placebo in reduction of incidence, time, and onset of UAE. Finally, the BENEDICT study found that albuminuria happened less frequently in patients taking trandolapril 2 mg daily and combination trandolapril 2 mg daily with verapamil SR 180 mg daily therapy as compared to placebo. That study found no difference between the groups taking verapamil SR 240 mg daily and placebo. The findings of all of the studies except for Chen et al. had a p value<0.05 and were significant. None of the aforementioned studies compared diuretic medications with other classes’ agents or even a placebo. Moreover, the authors of the reviews did not evaluate diuretics, so the placement of this group of drugs in the therapy has not been confirmed.

Treatment focused towards kidney protection in diabetic patients not only prevents nephropathy, but also affects cardiovascular complications. The exact mechanism is unknown, but it is believed that the decrease in glomerular filtration rate (GFR) causes inflammation and tubular injury, which leads to not only nephropathy, but also cardiovascular problems.

Further studies should be performed to evaluate the effectiveness of preventing nephropathy in diabetic patients with type 1 diabetes. Currently, in those patients, it is recommended to choose a blood pressure medication treatment based on their comorbidities.

Practice Pearls:

In type 2 diabetes patients with hypertension and normoalbuminuria, ACEIs and ARBs should be used first line, CCBs second line. For black patients, JNC recommends using calcium channel blockers or thiazide diuretic classes of medications because of the improved cardio protection.

In type 2 diabetes patients with hypertension and normoalbuminuria, the choice of the hypertensive agent should be based on other comorbidities they have.

Controlling blood pressure and glycemic levels are two other very important factors aside from eliminating proteinuria that help prevent developing nephropathy in diabetes patients.

Researched and prepared by Renata Kulawik, Doctor of Pharmacy Candidate LECOM College of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE